System and method for determining a stimulation threshold for closed loop spinal cord stimulation

ABSTRACT

System and methods are provided for determining a stimulation threshold for closed loop spinal cord stimulation (SCS). The system and methods provide a lead coupled to an implantable pulse generator (IPG). The system and methods deliver SCS pulses from the IPG to the lead electrodes in accordance with an SCS therapy and determine an evoked compound action potential (ECAP) amplitude based on an ECAP waveform resulting from the SCS therapy. The system and methods increase the SCS therapy by increasing at least one of an amplitude, a duration, and number of the SCS pulses associated with the SCS therapy. The system and methods also include iteratively repeat the delivering, determining and increasing operations until the ECAP amplitude exhibits a downward trend divergence. The system and methods define a stimulation threshold based on the ECAP amplitude at the trend divergence.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 16/359,790 filed Mar. 20, 2019 and entitled “SYSTEM AND METHODFOR DETERMINING A STIMULATION THRESHOLD FOR CLOSED LOOP SPINAL CORDSTIMULATION,” which is a continuation of U.S. patent application Ser.No. 15/345,163 filed Nov. 7, 2016 and entitled “SYSTEM AND METHOD FORDETERMINING A STIMULATION THRESHOLD FOR CLOSED LOOP SPINAL CORDSTIMULATION,” which issued May 7, 2019 as U.S. Pat. No. 10,279,182, thedisclosures of which are incorporated by reference herein in theirentirety.

FIELD OF THE INVENTION

Embodiments of the present disclosure generally relate toneurostimulation (NS) systems generating electric pulses proximate tonervous tissue, and more particularly to spinal cord stimulation (SCS)systems.

BACKGROUND OF THE INVENTION

NS systems are devices that generate electrical pulses and deliver thepulses to nervous tissue to treat a variety of disorders. For example,SCS has been used to treat chronic and intractable pain. Another exampleis deep brain stimulation, which has been used to treat movementdisorders such as Parkinson's disease and affective disorders such asdepression. While a precise understanding of the interaction between theapplied electrical energy and the nervous tissue is not fullyappreciated, it is known that application of electrical pulsesdepolarize neurons and generate propagating action potentials intocertain regions or areas of nerve tissue. The propagating actionpotentials effectively mask certain types of pain transmitted fromregions, increase the production of neurotransmitters, or the like. Forexample, applying electrical energy to the spinal cord associated withregions of the body afflicted with chronic pain can induce “paresthesia”(a subjective sensation of numbness or tingling) in the afflicted bodilyregions. Inducing this artificial sensation replaces the feeling of painin the body areas effectively masking the transmission of non-acute painsensations to the brain.

Aβ sensory fibers mediate sensations of touch, vibration, and pressurefrom the skin. Aβ sensory fibers have been shown to be recruited attherapeutic stimulation levels and the amplitude of the Aβ potentialcorrelates with the degree of coverage of the painful area or region.Further, the amplitude of the Aβ potential has been shown to increasewith increasing stimulation current from the SCS. At high currents,additional late responses have been observed.

A concern of SCS system designs are neural damage caused by thegenerated electrical pulses emitted from lead electrodes of the SCSsystem. Conventional SCS systems are configured such that the leadelectrodes are charge-balanced after the electrical pulses are emitted.However, an electrode may be polarized during deliver of the pulse thatirreversible tissue damage or electrode damage can occur. Therefore, aneed remains to determine a limit for the current and charge densitiesof the generated electrical pulses that allow charge injection becompensated by reversible processes.

SUMMARY

In accordance with one embodiment, a method for determining astimulation threshold for closed loop spinal cord stimulation isdisclosed. The method includes providing a lead coupled to animplantable pulse generator (IPG). The lead includes at least one leadelectrode and is configured to be implanted at a target positionproximate to nerve tissue of interest The method also includesdelivering SCS pulses from the IPG to the lead electrodes in accordancewith an SCS therapy and determining an evoked compound action potential(ECAP) amplitude based on an ECAP amplitude waveform resulting from theSCS therapy. The method further includes increasing the SCS therapy byincreasing at least one of a pulse amplitude, a pulse duration, pulsefrequency, burst frequency, or frequency of SCS pulse associated withthe SCS therapy. The method also includes iteratively repeating thedelivering, determining and increasing operations until an increasingtrend in the ECAP amplitude exhibits a trend divergence. The methodincludes defining a stimulation threshold based on the ECAP amplitude atthe trend divergence.

Optionally, during the iterative operation of the method, the trenddivergence is exhibited when the ECAP amplitude during an Nth iterationof the delivering, determining and increasing operation is lower than ananticipated ECAP amplitude extrapolated based on ECAP trending duringthe previous iterations of the delivering, determining and increasingoperations.

In an embodiment, a method for determining a stimulation threshold forclosed loop spinal cord stimulation (SCS) is disclosed. The methodincludes providing a lead coupled to an implantable pulse generator(IPG). The lead includes at least one lead electrode and is configuredto be implanted at a target position proximate to nerve tissue ofinterest. The method also includes programming the IPG to deliver aseries of SCS pulses to form a plurality of SCS waveforms from the leadelectrodes. Each SCS waveform has a different stimulation amplitude. Themethod includes measuring evoked compound action potential (ECAP)waveforms resulting from the plurality of stimulation waveforms.Further, the method includes defining a stimulation threshold based onat least one of an amplitude, a maximum, a minimum, a slope (ascendingor descending), and time delay between onset of SCS and above fiducialpoints of the ECAP waveforms.

In an embodiment, a system comprising a lead having at least one pair oflead electrodes, one is cathode, the other is anode. The lead isconfigured to be implanted at a target position proximate to or withinnerve tissue of interest. The system includes an implantable pulsegenerator (IPG) coupled to the lead. The IPG is configured to deliver aseries of SCS pulses to the lead electrodes at a predeterminedamplitude. The system also includes a sensing circuitry configured tomeasure an evoked compound action potential (ECAP) waveform resultingfrom the SCS therapy, and a processor programed to operation, inresponse to instructions stored on a non-transient computer-readablemedium. The processor, in response to the instructions, determines anECAP amplitude based on the ECAP waveform and increases the SCS therapyby increasing at least one of a pulse amplitude, a pulse duration, apulse frequency, burst frequency and a frequency of SCS pulsesassociated with the SCS therapy. The processor, in response to theinstructions, also iteratively repeats the determine and increaseoperations until an increasing trend in the ECAP amplitude exhibits atrend divergence and defines a stimulation threshold based on the ECAPamplitude at the trend divergence.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a neurostimulation system, according to an embodimentof the present disclosure.

FIG. 2 is a flowchart of a method for closed loop spinal cordstimulation, according to an embodiment of the present disclosure.

FIG. 3 illustrates a lead placement for spinal cord stimulation of apatient, according to an embodiment of the present disclosure.

FIG. 4 is a graphical representation of a spinal cord stimulation pulsedelivered to a lead electrode based on a spinal cord stimulationtherapy, according to an embodiment of the present disclosure.

FIG. 5 is a graphical representation of a sensed evoked compound actionpotential at a sensing electrode proximate to a lead electrode,according to an embodiment of the present disclosure

FIG. 6A is a graphical representation of a spinal cord stimulation pulsewith increased amplitude in comparison to the spinal cord stimulationpulse in FIG. 4.

FIG. 6B is a graphical representation of a spinal cord stimulation withincreased frequency of SCS pulses in comparison to the spinal cordstimulation pulse in FIG. 4.

FIG. 6C is a graphical representation of a spinal stimulation pulse withincreased pulse width in comparison to the spinal cord stimulation pulsein FIG. 4.

FIG. 7 is a graphical representation of the relationship between spinalcord stimulation current level and evoked compound action potentialamplitudes, according to an embodiment of the present disclosure.

FIG. 8 is a graphical representation of evoked compound action potentialamplitude changes over time in response to a similar spinal cordstimulation pulse, according to an embodiment of the present disclosure.

FIG. 9 is a flowchart of a method for closed loop spinal cordstimulation, according to an embodiment of the present disclosure.

FIG. 10 is a graphical representation of spinal cord stimulation pulsesforming a plurality of spinal cord stimulation waveforms delivered to alead electrode, according to an embodiment of the present disclosure.

FIG. 11 is a graphical representation of evoked compound actionpotential waveforms, according to an embodiment of the presentdisclosure.

FIG. 12 are three graphical representations of evoked compound actionpotential waveforms, according to an embodiment of the presentdisclosure.

FIG. 13 is a graphical representation of a sensed electrical potentialconsisting of an artifact of spinal cord stimulation pulse and an evokedcompound action potential generated by a nerve tissue of interest.

FIG. 14 illustrates a block diagram of exemplary internal components ofan external device, according to an embodiment of the presentdisclosure.

DETAILED DESCRIPTION OF THE INVENTION

Embodiments described herein include closed-loop neurostimulation (NS)systems, and methods for determining or monitoring the maximal currentdensity based on closed loop spinal cord stimulation (SCS) systems. TheNS system uses sensed neurological signals, such as an evoked compoundactivation potential (ECAP) from an Aβ sensory fiber or spinal cord. Theclosed-loop NS system may include an implantable pulse generator (IPG),which includes an algorithm that defines stimulation levels for SCS. Theclosed loop NS system may further include stimulating and sensingfunctions of targeted nerves or spinal cord. The NS system mayautomatically analyze neuronal recording to estimate whether thedelivered SCS is tolerable by neuronal cells. The NS system mayautomatically adjust SCS when ECAP recordings suggest irreversibleneuronal tissue damage. The adjustment may include turning off SCS,reduce SCS amplitude, switch SCS to another configuration, or the like.

Additionally, at least one embodiment described herein automaticallymeasures the ECAP at fixed stimulation strength on a daily or weeklybasis and transmits the ECAP recordings to an external device. Thelongitudinal trend of ECAP in response to a spinal cord stimulationconfiguration may be used to assess the health state of the neuronalcells. A decrease in ECAP trend may suggest functional deterioration ofthe neuronal cells, thus provide guidance to adjust SCS configuration.

While multiple embodiments are described, still other embodiments of thedescribed subject matter will become apparent to those skilled in theart from the following detailed description and drawings, which show anddescribe illustrative embodiments of disclosed inventive subject matter.As will be realized, the inventive subject matter is capable ofmodifications in various aspects, all without departing from the spiritand scope of the described subject matter. Accordingly, the drawings anddetailed description are to be regarded as illustrative in nature andnot restrictive.

FIG. 1 depicts an NS system 100 that generates electrical pulses forapplication to tissue of a patient according to one embodiment. Forexample, the NS system 100 may be adapted to stimulate spinal cordtissue, peripheral nerve tissue, deep brain tissue, cortical tissue,cardiac tissue, digestive tissue, pelvic floor tissue, or any othersuitable nerve tissue of interest within a patient's body.

The NS system 100 includes an implantable pulse generator (IPG) 150 thatis adapted to generate electrical pulses for application to tissue of apatient. The IPG 150 typically comprises a metallic housing or can 159that encloses a controller 151, pulse generating circuitry 152, acharging coil 153, a battery 154, a far-field and/or near fieldcommunication circuitry 155, battery charging circuitry 156, switchingcircuitry 157, sensing circuitry 158, memory 161, and the like. Thecontroller 151 typically includes a microcontroller or other suitableprocessor for controlling the various other components of the device.Software code may be stored in memory 161 of the IPG 150 or integratedwith the controller 151 for execution by the microcontroller orprocessor to control the various components of the device.

The IPG 150 may comprise a separate or an attached extension component170. If the extension component 170 is a separate component, theextension component 170 may connect with a “header” portion of the IPG150 as is known in the art. If the extension component 170 is integratedwith the IPG 150, internal electrical connections may be made throughrespective conductive components. Within the IPG 150, electrical pulsesare generated by the pulse generating circuitry 152 and are provided tothe switching circuitry 157. The switching circuitry 157 connects tooutputs of the IPG 150. Electrical connectors (e.g., “Bal-Seal”connectors) within the connector portion 171 of the extension component170 or within the IPG header may be employed to conduct variousstimulation pulses. The terminals of one or more leads 110 are insertedwithin connector portion 171 or within the IPG header for electricalconnection with respective connectors. Thereby, the pulses originatingfrom the IPG 150 are provided to the leads 110. The pulses are thenconducted through the conductors of the lead 110 and applied to tissueof a patient via lead electrodes 111 a-d. Any suitable known or laterdeveloped design may be employed for connector portion 171.

The lead electrodes 111 a-d may be positioned along a horizontal axis102 of the lead 110 and are angularly positioned about the horizontalaxis 102 so the lead electrodes 111 a-d do not overlap. The leadelectrodes 111 a-d may be in the shape of a ring such that each leadelectrode 111 a-d continuously covers the circumference of the exteriorsurface of the lead 110. Each of the lead electrodes 111 a-d areseparated by non-conducting rings 112, which electrically isolate eachlead electrode 111 a-d from an adjacent lead electrode 111 a-d. Thenon-conducting rings 112 may include one or more insulative materialsand/or biocompatible materials to allow the lead 110 to be implantablewithin the patient Non-limiting examples of such materials includepolyimide, polyetheretherketone (PEEK), polyethylene terephthalate (PET)film (also known as polyester or Mylar), polytetrafluoroethylene (PTFE)(e.g., Teflon), or parylene coating, polyether bloc amides,polyurethane. The lead electrodes 111 a-d may be configured to emit thepulses in an outward radial direction proximate to or within astimulation target. The electrodes 111 a-d may also be configured toacquire electrical potential measurements (e.g., voltage, current) forthe sensory circuit 158, such as evoked compound activation potentials(ECAP) emitted from the stimulation target.

Optionally, the IPG 150 may have more than one lead 110 connected viathe connector portion 171 of the extension component 170 or within theIPG header. Additionally, or alternatively, the electrodes 111 a-d ofeach lead 110 may be configured separately to emit current pulses ormeasure the ECAP emitted from the stimulation target.

Additionally, or alternatively, the lead electrodes 111 a-d may be inthe shape of a split or non-continuous ring such that the pulse may bedirected in an outward radial direction adjacent to the lead electrodes111 a-d. Examples of a fabrication process of the lead electrodes 111a-d is disclosed in U.S. Pat. No. 9,054,436, entitled “METHOD OFFABRICATING STIMULATION LEAD FOR APPLYING ELECTRICAL STIMULATION TOTISSUE OF A PATIENT,” which is expressly incorporated herein byreference.

It should be noted the lead electrodes 111 a-d may be in various otherformations, for example, in a planar formation on a paddle structure asdisclosed in U.S. patent application Ser. No. 14/198,260, filed Mar. 5,2014, entitled, “PADDLE LEADS FOR NEUROSTIMULATION AND METHOD OFDELIVERING THE SAME,” which is expressly incorporated herein byreference.

The lead 110 may comprise a lead body 172 of insulative material about aplurality of conductors within the material that extend from a proximalend of lead 110, proximate to the IPG 150, to its distal end. Theconductors electrically couple a plurality of the lead electrodes 111a-d to a plurality of terminals (not shown) of the lead 110. Theterminals are adapted to receive electrical pulses and the leadelectrodes 111 a-d are adapted to apply the pulses to the stimulationtarget of the patient. Also, sensing of physiological signals may occurthrough the lead electrodes 111 a-d, the conductors, and the terminals.It should be noted that although the lead 110 is depicted with four leadelectrodes 111 a-d, the lead 110 may include any suitable number of leadelectrodes 111 a-d (e.g., less than four, more than four) as well asterminals, and internal conductors. Additionally, or alternatively,various sensors (e.g., a position detector, a radiopaque fiducial) maybe located near the distal end of the lead 110 and electrically coupledto terminals through conductors within the lead body 172.

Although not required for all embodiments, the lead body 172 of the lead110 may be fabricated to flex and elongate upon implantation oradvancing within the tissue (e.g., nervous tissue) of the patienttowards the stimulation target and movements of the patient during orafter implantation. By fabricating the lead body 172, according to someembodiments, the lead body 172 or a portion thereof is capable ofelastic elongation under relatively low stretching forces. Also, afterremoval of the stretching force, the lead body 172 may be capable ofresuming its original length and profile. For example, the lead body maystretch 10°/o, 20%, 25%, 35%, or even up or above to 50% at forces ofabout 0.5, 1.0, and/or 2.0 pounds of stretching force. Fabricationtechniques and material characteristics for “body compliant” leads aredisclosed in greater detail in U.S. Provisional Patent Application No.60/788,518, entitled “Lead Body Manufacturing,” which is expresslyincorporated herein by reference. For implementation of the componentswithin the IPG 150, a processor and associated charge control circuitryfor an IPG is described in U.S. Pat. No. 7,571,007, entitled “SYSTEMSAND METHODS FOR USE IN PULSE GENERATION,” which is expresslyincorporated herein by reference. Circuitry for recharging arechargeable battery (e.g., battery charging circuitry 156) of an IPGusing inductive coupling and external charging circuits are described inU.S. Pat. No. 7,212,110, entitled “IMPLANTABLE DEVICE AND SYSTEM FORWIRELESS COMMUNICATION,” which is expressly incorporated herein byreference.

An example and discussion of “constant current” pulse generatingcircuitry (e.g., pulse generating circuitry 152) is provided in U.S.patent application Ser. No. 11/345,584, filed Jan. 31, 2006, entitled“PULSE GENERATOR HAVING AN EFFICIENT FRACTIONAL VOLTAGE CONVERTER ANDMETHOD OF USE,” which is expressly incorporated herein by reference. Oneor multiple sets of such circuitry may be provided within the IPG 150.Different pulses on different lead electrodes 111 a-d may be generatedusing a single set of the pulse generating circuitry 152 usingconsecutively generated pulses according to a “multi-stimset program” asis known in the art. Complex pulse parameters may be employed such asthose described in U.S. Pat. No. 7,228,179, entitled “Method andapparatus for providing complex tissue stimulation patterns,” andInternational Patent Publication Number WO 2001/093953 A1, entitled“NEUROMODULATION THERAPY SYSTEM,” which are expressly incorporatedherein by reference. Alternatively, multiple sets of such circuitry maybe employed to provide pulse patterns (e.g., tonic stimulation waveform,burst stimulation waveform) that include generated and deliveredstimulation pulses through various lead electrodes of one or more leads111 a-d as is also known in the art. Various sets of parameters maydefine the pulse characteristics and pulse timing for the pulses appliedto the various lead electrodes 111 a-d as is known in the art. Althoughconstant current pulse generating circuitry is contemplated for someembodiments, any other suitable type of pulse generating circuitry maybe employed such as constant voltage pulse generating circuitry.

The sensing circuitry 158 may measure an electric potential (e.g.,voltage, current) over time of the stimulation target or tissue throughat least one of the electrodes 111 a-d proximate to the stimulationtarget configured to measure the electrical potential. For example, thesensing circuitry 158 may measure an evoked compound activationpotential (ECAP) waveform from an Aβ sensory fiber or spinal cord.Optionally, the sensing circuitry 158 may store the electric potentialon the memory 161.

An external device 160 may be implemented to charge/recharge the battery154 of the IPG 150 (although a separate recharging device couldalternatively be employed), to access the memory 161, and to program theIPG 150 on the pulse specifications while implanted within the patient.Although, in alternative embodiments separate programmer devices may beemployed for charging and/or programming the NS system 100, the externaldevice 160 may be a processor-based system that possesses wirelesscommunication capabilities. Software may be stored within anon-transitory memory of the external device 160, which may be executedby the processor to control the various operations of the externaldevice 160. A “wand” 165 may be electrically connected to the externaldevice 160 through suitable electrical connectors (not shown). Theelectrical connectors may be electrically connected to a telemetrycomponent 166 (e.g., inductor coil, RF transceiver) at the distal end ofwand 165 through respective wires (not shown) allowing bi-directionalcommunication with the IPG 150. Optionally, in some embodiments, thewand 165 may comprise one or more temperature sensors for use duringcharging operations.

The user may initiate communication with the IPG 150 by placing the wand165 proximate to the NS system 100. Preferably, the placement of thewand 165 allows the telemetry system of the wand 165 to be aligned withthe far-field and/or near field communication circuitry 155 of the IPG150. The external device 160 preferably provides one or more userinterfaces 168 (e.g., touchscreen, keyboard, mouse, buttons, or thelike) allowing the user to operate the IPG 150. The external device 160may be controlled by the user (e.g., doctor, clinician) through the userinterface 168 allowing the user to interact with the IPG 150. The userinterface 168 may permit the user to move electrical stimulation alongand/or across one or more of the lead(s) 110 using different leadelectrode 111 a-d combinations, for example, as described in U.S. PatentPublished Application No. 2009/0326608, entitled “METHOD OF ELECTRICALLYSTIMULATING TISSUE OF A PATIENT BY SHIFTING A LOCUS OF STIMULATION ANDSYSTEM EMPLOYING THE SAME,” which is expressly incorporated herein byreference. Optionally, the user interface 168 may permit the user todesignate which electrodes 111 a-d are to stimulate (e.g., emit currentpulses, in an anode state, in a cathode state) the stimulation target,to measure the ECAP (e.g., connecting to the sensing circuitry 158)resulting from the current pulses, remain inactive (e.g., floating), orthe like. Additionally, or alternatively, the external device 160 mayaccess or download the electrical measurements from the memory 161acquired by the sensing circuitry 158.

Also, the external device 160 may permit operation of the IPG 150according to one or more spinal cord stimulation (SCS) programs ortherapy to treat the patient. Each SCS program may include one or moresets of stimulation parameters of the pulse including pulse amplitude,stimulation level, pulse width, pulse frequency or inter-pulse period,pulse repetition parameter (e.g., number of times for a given pulse tobe repeated for respective stimset during execution of program),biphasic pulses, monophasic pulses, etc. The IPG 150 modifies itsinternal parameters in response to the control signals from the externaldevice 160 to vary the stimulation characteristics of the stimulationpulses transmitted through the lead 110 to the tissue of the patient. NSsystems, stimsets, and multi-stimset programs are discussed In PCTPublication No. WO 01/93953, entitled “NEUROMODULATION THERAPY SYSTEM,”and U.S. Pat. No. 7,228,179, entitled “METHOD AND APPARATUS FORPROVIDING COMPLEX TISSUE STIMULATION PATTERNS,” which are expresslyincorporated herein by reference.

FIGS. 2 and 9 are flowcharts of a method 200 and 900, respectively, fordetermining a stimulation threshold for closed loop spinal cordstimulation. The methods 200 and 900, for example, may employ structuresor aspects of various embodiments (e.g., systems and/or methods)discussed herein. For example, an implantable pulse generator (IPG) maybe similar to the IPG 150 (FIG. 1) or may include other features, suchas those described or referenced herein. In various embodiments, certainsteps (or operations) may be omitted or added, certain steps may becombined, certain steps may be performed simultaneously, certain stepsmay be performed concurrently, certain steps may be split into multiplesteps, certain steps may be performed in a different order, or certainsteps or series of steps may be re-performed in an iterative fashion.Furthermore, it is noted that the following is just one possible methodof performing simultaneous burst and tonic stimulation. It should benoted, other methods may be used, in accordance with embodiments herein.

One or more methods may (i) provide a lead coupled to an implantablepulse generator (IPG), (ii) deliver spinal cord stimulation (SCS) pulsesfrom the IPG to the lead electrodes in accordance with an SCS therapy,(iii) determine an evoked compound action potential (ECAP) amplitudebased on an ECAP waveform resulting from the SCS therapy, (iv) increasethe SCS therapy by increasing at least one of an amplitude, a durationand a number of the SCS pulses associated with the SCS therapy, (v)iteratively repeat the delivering, determining and increasing operationsuntil the ECAP amplitude exhibits a trend divergence, and (vi) defininga stimulation threshold based on the ECAP amplitude at the trenddivergence.

Beginning at 202, the method 200 provides a lead 304 coupled to animplantable pulse generator (IPG) 308. FIG. 3 is an illustration of alead placement 300 for SCS. The lead 304 is positioned at a targetposition, in an epidural space 302, of a patient so as to be in closeproximity to a nerve tissue of interest, a spinal cord 306. The lead 304includes eight electrodes 311 a-h that are each separated bynon-conducting rings 312. The lead 304 is connected via a lead body 310to the IPG 308. It should be noted, that in alternative embodiments thelead 304 may have a fewer than or greater than the number of leadelectrodes 311 a-h shown in FIG. 3. For example, the lead 304 may have asingle lead electrode 311 a used in conjunction with the can (e.g., thecan 159) during the SCS pulses in a cathode or anode state.

At 204, the method 200 delivers spinal cord stimulation (SCS) pulses 406from the IPG 308 to lead electrodes 311 a-h in accordance with an SCStherapy. The IPG may be programmed to deliver SCS pulses to the leadelectrodes 311 a-h through the lead body 310 at a predeterminedamplitude. For example, the IPG 150 may be programmed or receivestimulation programs representing the SCS therapy from the externaldevice 160. The SCS therapy may include different SCS waveforms formedby the SCS pulses 406, such as a burst stimulation waveform, a tonicstimulation waveform, a biphasic pulse, or the like, which are emittedfrom one or more of the lead electrodes 311 a-h. The SCS therapy mayinclude predetermined electrical characteristics of the SCS pulses 406,such as, amplitude 410, 412, duration (e.g., pulse width) 414, 416, andnumber of the SCS pulses for each SCS waveform.

FIG. 4 illustrates a series of SCS pulses 406 delivered by the IPG 308and emitted by one or more of the lead electrodes 311 a-h at apredetermined amplitude (e.g., a positive amplitude 412, a negativeamplitude 410) and duration 414, 416 in accordance with an embodiment. Ahorizontal axis 402 represents time, and a vertical axis 404 mayrepresent voltage or electrical potential. For example, the SCS pulses406 may be emitted from the lead electrode 311 e, which is configured ina cathode state (e.g., electrically coupled to the common ground), andthe lead electrodes 311 d and 311 f, which are configured in an anodestate (e.g., electrically coupled to the battery 154). It should benoted that the SCS pulses 406 may be generated by more lead electrodes311 a-h, fewer lead electrodes 311 a-h, and/or other combinations oflead electrodes 311 a-h of the lead 304. The series of SCS pulses 406form a SCS waveform, such as a tonic or biphasic stimulation waveform.It should be noted that in other embodiments the SCS pulses 406 may formother SCS waveforms (e.g., burst stimulation waveform). It should benoted that although the amplitudes 410 and 412 are shown being equal inmagnitude, alternative embodiments may not. For example, the positiveamplitude 412 may have a greater amplitude than the negative amplitude410. It should be noted that although the durations 414 and 416 of theSCS pulses 406 am shown being equal in length (e.g., pulse width),alternative embodiments may not. For example, the duration 414 of theSCS pulse 406 corresponding to the positive amplitude 412 may be longeror shorter in length (e.g., pulse width) than the duration 416 of theSCS pulse 406 corresponding to the negative amplitude 410.

At 206, the method 200 determines an ECAP amplitude 510 based on an ECAPwaveform 502 resulting from the ECAP therapy. FIG. 5 is a graphicalrepresentation 500 of an ECAP waveform 502 measured proximate to thenerve tissue of interest (e.g., the spinal cord 308, Aβ sensory fibers).A horizontal axis 504 represents time, and a vertical axis 506 mayrepresent voltage or electrical potential. The sensing circuitry 158 mayacquire the ECAP waveform 502, resulting from the SCS pulses 406, bymeasuring a voltage or electrical potential of one or more of the leadelectrodes 311 a-h proximate to the nerve tissue of interest. Thesensing circuitry 158 may utilize one or more of the lead electrodes 311a-h to measure the ECAP waveform 502. Optionally, the sensing circuitry158 may measure the ECAP waveform 502 utilizing one or more combinationsof electrodes 311 a-h. In at least one embodiment, the ECAP waveform 502may be stored by the controller 151 or sensing circuitry 158 to thememory 161, for example, onto a stimulation database with thecorresponding electrical specifications (e.g., amplitude, frequency,waveform configuration, duration, number of SCS pulses 406) of the SCSpulses 406. Additionally, or alternatively, the ECAP waveforms may betransmitted by the communication circuitry 155 to the external device160.

The ECAP amplitude 510 may be determined by the controller 151 based ona peak 512 during a predetermined time period 514 of the ECAP waveform502 with respect to a baseline 516 (e.g., common ground of the NS system100). The ECAP amplitude 510 may be stored by the controller 151 to thememory 161, for example, onto the stimulation database. Optionally, theECAP amplitude 510 may be transmitted to the external device 160 by thecommunication circuitry 155. The predetermine time period 514 may bebased on when the SCS pulse is emitted from the electrodes 311 a-h. Forexample, the predetermined time period 514 may be based on a set amountof time, such as 1.3 ms, after the SCS pulses 406. It should be notedthat in other embodiments the set amount of time may be less than orgreater than 1.3 ms.

At 208, the method 200 increases the SCS therapy by increasing at leastone of the amplitude 414, 416, the duration 414, 416, and the number ofSCS pulses 406 associated with the SCS therapy. For example, thecontroller 151 may increase at least one of the characteristics (e.g.,the amplitude 414, 416, the duration 414, 416, and the number of SCSpulses 406) of the SCS pulses 406 delivered by the IPG 308. FIGS. 6A-Care graphical representations of SCS pulses 606 a-c with increased SCStherapies relative to the SCS pulses 406 from FIG. 4. A horizontal axis612 represents time, and a vertical axis 608 may represent voltage orelectrical potential.

FIG. 6A illustrates SCS pulses 606 a with an increased amplitude 610 and616 over the amplitudes 414 and 416 of the SCS pulses 406. It should benoted that in other embodiments the duration 414, the duration 416and/or the number of the SCS pulses 606 a may be increased as well. Itshould be noted that although the amplitudes 610 and 616 are shown beingincreased in equal magnitude, alternative embodiments may not. Forexample, the positive amplitude 610 may have a greater amplitude thanthe negative amplitude 616.

FIG. 68 illustrates SCS pulses 606 b with an increased number of SCSpulses 606 b relative to the SCS pulses 406. It should be noted that inother embodiments the duration 414, the duration 416, the amplitude 410and/or the amplitude 412 of the SCS pulses 606 b may be increased aswell.

FIG. 6C illustrates SCS pulses 606 c with an increased duration 618 and620 (e.g., pulse width) relative to the duration 414 and 416 of the SCSpulses 406. It should be noted that in other embodiments the amplitude410 and 412 and/or number of the SCS pulses 606 c may be increased aswell. It should be noted that although the durations 618 and 620 areshown being increased in equal magnitude, alternative embodiments maynot. For example, the duration 618 may be longer than the duration 620.

At 210, the method 200 determines whether the ECAP amplitude 716exhibits a trend divergence 732. FIG. 7 is a graphical representation700 of ECAP amplitudes 716 plotted over amplitudes (e.g., the positiveamplitude 412, the negative amplitude 410, the positive amplitude 610,the negative amplitude 616) of the SCS pulses (e.g., SCS pulses 406, 606a-c) along the horizontal axis 704. It should be noted that in otherembodiments, the ECAP amplitudes 716 may be plotted over the duration(e.g., the pulse width) and/or number of the SCS pulses. A vertical axis706 represents a voltage or electrical potential magnitude of the ECAPamplitudes 716. The controller 151 may compare ECAP amplitudes 716 at agiven SCS current level over ECAP amplitudes at lower SCS current levelsto identify or determine whether a trend divergence 732, such as adownward trend divergence, is exhibited by the ECAP amplitudes 716.

The graphical representation 700 includes an ECAP amplitude line graph702 illustrating the non-linear relationship between the amplitudes ofthe SCS pulses and the ECAP amplitudes 716, which may be characterizedin phases I-IV transitioning at current amplitudes at 720, 724 and 726.

For example, in phase I the ECAP amplitudes 716 remain approximatelyparallel to the horizontal axis 704. In phase II, when the currentamplitudes are between 724 and 726, the ECAP amplitudes 716 increase(e.g., positive slope) in a linear fashion. In phase III, when thecurrent amplitude are between 720 and 726, the ECAP amplitudes 716 reacha plateau and are approximately parallel to the horizontal axis 704. Inphase IV, when the current amplitudes are above 720 (e.g., thestimulation threshold 734), the ECAP amplitudes 716 start to decrease orenter a break down region, which indicate overstimulation and impairedneuronal functions of the nerve tissue of interest. The transition fromphase III to phase IV may occur around a divergence inflection point orpoint of trend divergence, such as a downward trend divergence,corresponding to a sign (e.g., from positive to negative, from near zeroto negative) change of the slope of the ECAP amplitude line graph 702.For example, the divergence inflection point corresponds to the onset ofa negative slope of the ECAP amplitude line graph 702.

The controller 151 may identify the trend divergence by iterativelydeliver (e.g., the method 200 at 204), determine (e.g., the method 200at 206) and increase (e.g., the method 200 at 208) operations toascertain the stimulation threshold 734 that corresponds to the start ofphase IV (e.g., the divergence inflection point). For example, thecontroller 151 determines the ECAP amplitude 716 b having a voltage at710 from the sensor circuitry 158 measurements of the corresponding ECAPwaveform. The ECAP amplitude 716 b may be the result of the SCS pulses406. The controller 151 compares the ECAP amplitude 716 b with theprevious ECAP amplitude, the ECAP amplitude 716 a, stored on the memory161. The ECAP amplitude 716 a has a voltage at 708. The controller 151determines, based on the voltages 708-710, that the ECAP amplitude 716 bis greater than the ECAP amplitude 716 a, and increases the SCS therapyby, for example, increasing the amplitude 410 and 412 of the SCS pulses406 to attain an amplitude of the SCS pulses at 718. In at least oneembodiment, the controller 151 may increase the SCS therapy at a rate ora predetermined amount. Optionally, the increase or adjustment of theSCS therapy may be received by the IPG 308 from the external device 160.

If, at 210, the ECAP amplitude 716 does not exhibit the trend divergence732, for example, determined by the controller 151, the method 200returns to 204 to deliver the SCS pulses (e.g., the SCS pulses 606 a-c)from the IPG 308 to the same stimulation location (e.g. electrodes 311a-h) in accordance with the increased SCS therapy previously increasedat 208.

The controller 151 may repeat the above process until the ECAP amplitude716 exhibits the trend divergence 732 (e.g., decrease In ECAP amplitude716 after an increasing trend and/or a plateau in the ECAP amplitudesindicating that the ECAP amplitude 716 is in phase IV). Optionally, thetrend divergence 732 is exhibited when the ECAP amplitude 716 during anNth iteration of the delivering (e.g., at 204 of the method 200),determining (e.g., at 206 of the method 200) and increasing (e.g., at208 of the method 200) operations is lower than the ECAP amplitude 716during an N−1 iteration or a plurality of previous iterations of thedelivering, determining and increasing operations.

For example, the controller 151 determines, during the thirteenthiteration of the method 200, the ECAP amplitude 716 e has a voltagepotential at 728. The ECAP amplitude 716 e is the result of SCS pulses(e.g., the SCS pulses 606 a) having amplitudes at 722. The controller151 compares the ECAP amplitude 716 e with a plurality or severalprevious iterations, such as the tenth, eleventh, and twelfthiterations, which may be stored on the memory 161. For example, duringthe twelfth iteration the controller 151 determined the ECAP amplitude716 d had a voltage at 730. The controller 151 compares the voltages728-730 of the ECAP amplitudes 716 d-e. The controller 151 determinesthat the ECAP amplitude 716 e is lower than the ECAP amplitude 716 d.The controller 151 may determine that the ECAP amplitude 716 e exhibitsthe trend divergence 732 if the ECAP amplitudes of the plurality ofprevious iterations are each greater than the ECAP amplitude 716 e.Additionally or alternatively, the controller 151 may calculate anaverage ECAP amplitude from the previous iterations, which is comparedwith the ECAP amplitude 716 e. It should be noted that the number ofprevious iteration may be greater than or less than three.

Optionally, the controller 151 may compare the amplitude differencesbetween the ECAP amplitude 716 d and the ECAP amplitude 716 e with athreshold. For example, the controller 151 may determine that the ECAPamplitude 716 e is lower than the ECAP amplitude 716 d if the ECAPamplitude 716 e is lower than the ECAP amplitude 716 d by at least thethreshold. Optionally, the threshold may be predetermined value storedon the memory 161 and/or received by the external device 160.Additionally, or alternatively, the threshold may be based on theplurality of ECAP amplitudes corresponding to an average differencebetween two select concurrent ECAP amplitudes from the plurality of ECAPamplitudes.

If at 210, the ECAP amplitude 716 does exhibit the trend divergence 732,then at 212, the stimulation threshold 734 is defined based on the ECAPamplitude 716 e at the trend divergence 732. For example, the controller151 determines that the ECAP amplitude 716 e exhibits the trenddivergence 732. The ECAP amplitude 716 e resulted from the SCS therapyhaving SCS pulses (e.g., the SCS pulses 608 a) with amplitudes at 720.Based on the ECAP amplitude 716 e, the controller 151 defines thestimulation threshold 734 at the SCS pulse amplitude 720 that resultedin the ECAP amplitude 716 e.

The stimulation threshold 734 may be used by the controller 151 to limitthe amplitude of the SCS pulses during the SCS therapy. For example, thecontroller 151 may have the IPG 308 deliver SCS pulses with amplitudesat or below the stimulation threshold 734. It should be noted that inother embodiments the stimulation threshold 734 may not be defined bythe amplitude of the SCS pulses, for example, defined by the durationand/or number of the SCS pulses. Additionally, or alternatively, thestimulation threshold 734 may be defined by combinations of electricalcharacteristics of the SCS pulses, for example, the stimulationthreshold 734 may define the duration and amplitude of the SCS pulses,the number and amplitude of the SCS pulses, and the like.

Optionally, the method 200 may include transmitting an alertnotification once the stimulation threshold 734 is defined. For example,the controller 151 may instruct the communication circuitry 155 totransmit an alert notification to the external device 160.

Optionally, the method 200 may define a suprathreshold zone and asubthreshold zone based on the stimulation threshold 734 for the SCSpulses 406. For example, once the stimulation threshold 734 is definedthe controller 151 may define the suprathreshold zone by asuprathreshold predetermined value (e.g., 5 mA) above the stimulationthreshold 734. The subthreshold zone may be defined by a subthresholdpredetermined value (e.g., 5 mA) below the stimulation threshold 734.

Optionally, the method 200 may include delivering a series of SCS pulses(e.g., the SCS pulses 406) that have an amplitude at or below thestimulation threshold 734, once the stimulation threshold 734 is definedat 212. Additionally, the method 200 may reduce the stimulationthreshold 734 when an instantaneous ECAP amplitude 812 a is lower thanan averaged ECAP amplitude 814. FIG. 8 is a line graph 800 of ECAPamplitudes 812 plotted over time along the horizontal axis 802. Avertical axis 804 represents a voltage or electrical potential of theECAP amplitudes 812 in response to a fixed SCS stimulation at differenttimes, for example, the repeated SCS pulses have the same amplitude(e.g., current), frequency, or the like. The ECAP amplitudes 812 may bebased on ECAP waveforms (e.g., the ECAP waveform 502) resulting from SCSpulses having an amplitude at or below the stimulation threshold 734delivered by the IPG 308.

The averaged ECAP amplitude 814 may be based on one or more previouslymeasured ECAP amplitudes (e.g., the ECAP amplitudes 812) measured by theIPG 308. The controller 151 may continually calculate an average ECAPamplitude based on previously measured ECAP amplitudes 812. For example,the ECAP amplitudes 812, before the time 810, have an averaged ECAPamplitude at 814.

After the time 810, the ECAP amplitudes 812 decrease. The controller 151may identify the decrease in ECAP amplitudes 812 by comparing theinstantaneous ECAP amplitude 812 a and the averaged ECAP amplitude 814based on the previous ECAP amplitude measurements. Optionally, thecontroller 151 may compare the difference between the ECAP amplitude 812a and the averaged ECAP amplitude 814 with a predetermined threshold816. Once the controller 151 determines that the ECAP amplitude 812 isdecreasing, the controller 151 may reduce the stimulation threshold 734.Optionally, the controller 151 may reduce the stimulation threshold 734by a predetermined amount. Optionally, the controller 151 may change theconfiguration of the SCS pulses, for example, from a tonic stimulationwaveform to a burst stimulation waveform. Optionally, the controller 151may adjust the duration and/or number of the SCS pulses. Additionally,or alternatively, the controller 151 may have the IPG 308 stopdelivering the SCS pulses to the lead electrodes 311 a-h. Optionally,the controller 151 may instruct the communication circuitry 155 totransmit an alert notification to the external device 160.

Optionally, the method 200 may include determining a stimulationbaseline for the SCS pulses 406 based on a change in amplitude of theECAP waveform 502. The stimulation baseline indicates the currentamplitude at 724, which is the transition boundary between phase I andII shown in FIG. 7. The stimulation baseline indicates a minimumamplitude of the SCS pulses that will recruit neurons at the nervetissue of interest. Recruitment of the neurons is shown as the increasein the ECAP amplitudes 816 after the current amplitude at 724. Thecontroller 151 may determine the stimulation baseline when the ECAPamplitude 816 increases a predetermined amount during the iterativeprocess described above, for example, when comparing the ECAP amplitude716 a with the ECAP amplitude 716 c to determine whether the ECAPamplitude exhibits a trend divergence.

One or more methods may (i) provide a lead coupled to the IPG, (ii)program the IPG to deliver spinal cord stimulation (SC S) pulses to forma plurality of SCS waveforms from the lead electrodes, (iii) measureECAP waveforms resulting from the plurality of SCS waveforms, and (iv)define a stimulation threshold based on at least one of an amplitude, aslope (ascending or descending), a maximum, a minimum, or time delaybetween the onset of SCS and above one or more fiducial points of theECAP waveforms.

Beginning at 902, the method 900 provides a lead 304 coupled to animplantable pulse generator (IPG) 308.

Next at 904, the IPG 308 is programmed to deliver SCS pulses 1000 to thelead electrodes 311 a-h to form a plurality of SCS waveforms 1016-1024from the lead electrodes 311 a-h. FIG. 10 illustrates a series of SCSpulses 1000 delivered by the IPG 308 and emitted by the lead electrodes311 a-h at various predetermined stimulation amplitudes 1004-1012increasing over time, in accordance with an embodiment A horizontal axis1014 represents time, and a vertical axis 1002 may represent voltage orelectrical potential. The series of SCS pulses 1000 form SCS waveforms1016-1024 illustrated as tonic or biphasic stimulation waveforms.However, it should be noted that in other embodiments the SCS pulses1000 may form other SCS waveforms (e.g., burst stimulation waveform).

At 906, ECAP waveforms 1104-1112 resulting from the plurality of SCSwaveforms 1016-1024 are measured, for example, by the sensor circuitry158. FIG. 11 is a graphical representation 1100 of the ECAP waveforms1104-1112 measured proximate to the nerve tissue of interest (e.g., thespinal cord 308, Aβ sensory fibers). The ECAP waveforms 1104-1112 areshown aligned based on peaks 1124-1132 of each ECAP waveforms1104-11120. A horizontal axis 1122 represents time, and a vertical axis1120 may represent voltage or electrical potential. The sensingcircuitry 158 may acquire the ECAP waveforms 1100, resulting from theplurality of SCS waveforms 1016-1024, by measuring a voltage orelectrical potential of one or more of the lead electrodes 311 a-hproximate to the nerve tissue of interest. The sensing circuitry 158 mayutilize one or more of the lead electrodes 311 a-h to measure the ECAPwaveforms 1104-1112. Each of the ECAP waveforms 1104-1112 correspond toone of the SCS waveforms 1016-1024, respectively. For example, the ECAPwaveform 1104 corresponds to the SCS waveform 1016; the ECAP waveform1106 corresponds to the SCS waveform 1018; the ECAP waveform 1108corresponds to the SCS waveform 1020; the ECAP waveform 1110 correspondsto the SCS waveform 1022; and the ECAP waveform 1112 corresponds to theSCS waveform 1024.

At 908, the method 900 determines slopes 1208-1212 for each ECAPwaveform 1104-1112. FIG. 12 illustrates three graphical representations1202-1206, from the graphical representation 1100 shown in FIG. 11, ofthe ECAP waveforms 1108-1112, respectively. The controller 151 maydetermine the slopes 1208-1212 for each ECAP waveform 1108-1112 based ona predetermined baseline 1214 and the peak 1124-1132 of the ECAPwaveform 1104-1112. The slopes 1208-1212 may represent a ratio of thevoltage change (e.g., vertical axis 1120) and the change in time (e.g.,horizontal axis 1122) of the ECAP waveform 1104-1112 at thepredetermined baseline 1220-1224 to the peaks 1130, 1132, and 1128,respectively. The predetermined baseline 1214 may be the common groundof the NS system 100. Optionally, the predetermined baseline 1214 may bereceived by the IPG 308 from the external device 160.

At 910, the method 900 determines a time delay between the onset of SCS(e.g., a stimulation spike 1314) and above one or more fiducial points1312 for each of the ECAP waveforms 1104-1112. FIG. 13 is a graphicalrepresentation 1300 of electrical potential measurements of the nervetissue of interest at a lead electrode (e.g., one of the lead electrodes311 a-h) for an ECAP waveform 1310 representing one of the ECAPwaveforms 1104-1112. A horizontal axis 1302 represents time, and avertical axis 1304 may represent voltage or electrical potential. An SCSwaveform 1308, configured as a tonic stimulation waveform, is emittedfrom the lead electrode. After the SCS waveform 1308, the ECAP waveform1310 is measured utilizing the sensing circuitry 158. The ECAP waveform1310 includes a stimulation spike 1314 corresponding to the onset of theSCS and a minimum peak of the ECAP waveform 1310. The minimum peak maybe assigned by the controller as the fiducial point 1312 for determiningthe time delay. It should be noted that in other embodiments more thanone fiducial point may be assigned based on a maximum peak, maximum orminimum slope, a morphology point of interest of the ECAP waveform 1310,or the like. The controller 151 may calculate the time delay 1306between the stimulation spike 1314 and the fiducial point 1312 (e.g.,the minimum peak) of the ECAP waveform 1310.

Next at 912, a stimulation threshold is defined based on a stimulationamplitude and at least one of an amplitude, the slope (ascending ordescending), a maximum, a minimum, or time delay between the onset ofthe SCS and above one or more fiducial point of the ECAP waveforms. Forexample, the controller 151 may compare the time delays (e.g., the timedelay 1306) of each the ECAP waveforms 1104-1112 and determine anincrease in the time delay beyond a predetermined threshold indicatesthat the stimulation threshold has been reached. The controller 151 maydefine the stimulation amplitude, corresponding to the SCS waveform(e.g., such as the stimulation amplitude) resulting in the increasedtime delay, as the stimulation threshold.

In at least one embodiment, the controller 151 may determine a decreasein the magnitude of the slope 1208-1212 corresponds to overstimulationof the neurons of the nerve tissue of interest indicating that thestimulation threshold has been reached. For example, the ECAP waveforms1108-1112 each correspond to the SCS waveforms 1020-1024 with differentpredetermined stimulation amplitudes 1008-1012. The controller 151compares the slopes 1208 and 1210, and the slopes 1210 and 1212resulting from the SCS waveforms 1020-1024 having predeterminedstimulation amplitudes 1008-1012, respectively. The controller 151determines that the magnitude of the slope 1210 is greater than themagnitude of the slope 1208. The controller 151 determines that themagnitude of the slope 1212 is lower than the magnitude of the slope1210, indicating overstimulation. The controller 151 defines thestimulation threshold as the predetermined stimulation amplitude 1010,which corresponds to the SCS waveform 1022 resulting in the ECAPwaveform 1110 (e.g., prior to the reduced magnitude of slope 1212).Optionally, the controller 151 may determine the stimulation thresholdhas been reached when the magnitude of slope is reduced by apredetermined threshold.

FIG. 14 illustrates a functional block diagram of an external device1400, according to at least one embodiment, that is operated inaccordance with the processes described herein and to interface with theNS system 100 as described herein. The external device 1400 may be aworkstation, a portable computer, a tablet computer, a PDA, a cell phoneand the like. The external device 1400 includes an internal bus 1401that may connect/interface with a Central Processing Unit (“CPU”) 1402,ROM 1404, RAM 1406, a hard drive 1408, a speaker 1410, a printer 1412, aCD-ROM drive 1414, a floppy drive 1416, a parallel I/O circuit 1418, aserial I/O circuit 1420, the display 1422, a touchscreen 1424, astandard keyboard 1426, custom keys 1428, and an RF subsystem 1430. Theinternal bus 1401 is an address/data bus that transfers informationbetween the various components described herein. The hard drive 1408 maystore operational programs as well as data, such as stimulation waveformtemplates and detection thresholds.

The CPU 1402 typically includes a microprocessor, a microcontroller, orequivalent control circuitry, designed specifically to controlinterfacing with the external device 1400 and with the NS system 100.The CPU 1402 may include RAM or ROM memory, logic and timing circuitry,state machine circuitry, and I/O circuitry to interface with the NSsystem 100. The display 1422 (e.g., may be connected to the videodisplay 1432). The display 1422 displays various information related tothe processes described herein. The touchscreen 1424 may display graphicinformation relating to the NS system 100 (e.g., stimulation levels, SCSwaveforms, ECAP measurements, the SCS therapy applied) and include agraphical user interface. The graphical user interface may includegraphical icons, scroll bars, buttons, and the like which may receive ordetect user or touch inputs 1434 for the external device 1400 whenselections are made by the user. Optionally the touchscreen 1424 may beintegrated with the display 1422. The keyboard 1426 (e.g., a typewriterkeyboard 1436) allows the user to enter data to the displayed fields, aswell as interface with the RF subsystem 1430. Furthermore, custom keys1428, for example, may turn on/off the external device 1400. The printer1412 prints copies of reports 1440 for a physician to review (e.g., ECAPwaveforms) or to be placed in a patient file, and the speaker 1410provides an audible warning (e.g., sounds and tones 1442) to the user.The parallel I/O circuit 1418 interfaces with a parallel port 1444. Theserial I/O circuit 1420 interfaces with a serial port 1446. The floppydrive 1416 accepts diskettes 1448. Optionally, the serial I/O port maybe coupled to a USB port or other interface capable of communicatingwith a USB device such as a memory stick. The CD-ROM drive 1414 acceptsCD ROMs 1450.

The RF subsystem 1430 includes a central processing unit (CPU) 1452 inelectrical communication with an RF circuit 1454, which may communicatewith both memory 1456 and an analog out circuit 1458. The analog outcircuit 1458 includes communication circuits to communicate with analogoutputs 1464. The external device 1400 may wirelessly communicate withthe NS system 100 using a telemetry system. Additionally, oralternatively, the external device 1400 may wirelessly communicate withthe NS system 100 utilize wireless protocols, such as Bluetooth,Bluetooth low energy, WiFi, MICS, and the like. Alternatively, ahard-wired connection may be used to connect the external device 1400 tothe NS system 100.

Optionally, the external device 1400 may transmit a stimulation databaserequest to the IPG 150. For example, the user may instruct the externaldevice 1400 to transmit the stimulation database request from thegraphical user interface on the touchscreen 1424, the keyboard 1426, orthe like. The NS system 100 receives the request via the communicationcircuitry 155 and transmits the stimulation database stored on thememory 161 to the external device 1400.

The controllers 151, the CPU 1402, and the CPU 1452 may include anyprocessor-based or microprocessor-based system including systems usingmicrocontrollers, reduced instruction set computers (RISC), applicationspecific integrated circuits (ASICs), field-programmable gate arrays(FPGAs), logic circuits, and any other circuit or processor capable ofexecuting the functions described herein. Additionally, oralternatively, the controllers 151, the CPU 1402, and the CPU 1452 mayrepresent circuit modules that may be implemented as hardware withassociated instructions (for example, software stored on a tangible andnon-transitory computer readable storage medium, such as a computer harddrive, ROM, RAM, or the like) that perform the operations describedherein. The above examples are exemplary only and are thus not intendedto limit in any way the definition and/or meaning of the term“controller.” The controllers 151, the CPU 1402, and the CPU 1452 mayexecute a set of instructions that are stored in one or more storageelements, in order to process data. The storage elements may also storedata or other information as desired or needed. The storage element maybe in the form of an information source or a physical memory elementwithin the controllers 151, the CPU 1402, and the CPU 1452. The set ofinstructions may include various commands that instruct the controllers151, the CPU 1402, and the CPU 1452 to perform specific operations suchas the methods and processes of the various embodiments of the subjectmatter described herein. The set of instructions may be in the form of asoftware program. The software may be in various forms such as systemsoftware or application software. Further, the software may be in theform of a collection of separate programs or modules, a program modulewithin a larger program or a portion of a program module. The softwarealso may include modular programming in the form of object-orientedprogramming. The processing of input data by the processing machine maybe in response to user commands, or in response to results of previousprocessing, or in response to a request made by another processingmachine.

It is to be understood that the subject matter described herein is notlimited in its application to the details of construction and thearrangement of components set forth in the description herein orillustrated in the drawings hereof. The subject matter described hereinis capable of other embodiments and of being practiced or of beingcarried out in various ways. Also, it is to be understood that thephraseology and terminology used herein is for the purpose ofdescription and should not be regarded as limiting. The use of“including,” “comprising,” or “having” and variations thereof herein ismeant to encompass the items listed thereafter and equivalents thereofas well as additional items.

It is to be understood that the above description is intended to beillustrative, and not restrictive. For example, the above-describedembodiments (and/or aspects thereof) may be used in combination witheach other. In addition, many modifications may be made to adapt aparticular situation or material to the teachings of the inventionwithout departing from its scope. While the dimensions, types ofmaterials and coatings described herein are intended to define theparameters of the invention, they are by no means limiting and areexemplary embodiments. Many other embodiments will be apparent to thoseof skill in the art upon reviewing the above description. The scope ofthe invention should, therefore, be determined with reference to theappended claims, along with the full scope of equivalents to which suchclaims are entitled. In the appended claims, the terms “including” and“in which” are used as the plain English equivalents of the respectiveterms “comprising” and “wherein.” Moreover, in the following claims, theterms “first,” “second,” and “third,” etc. are used merely as labels,and are not intended to impose numerical requirements on their objects.Further, the limitations of the following claims are not written inmeans-plus-function format and are not intended to be interpreted basedon 35 U.S.C. § 112(f), unless and until such claim limitations expresslyuse the phrase “means for” followed by a statement of function void offurther structure.

1-20. (canceled)
 21. A method for determining a stimulation thresholdfor closed loop spinal cord stimulation (SCS), the method comprising:delivering a series of SCS pulses from at least one lead electrode of alead coupleable to an implantable pulse generator (IPG) having aprocessor, the at least one lead electrode configured to be implanted ata target position proximate to or within nerve tissue of interest, theseries of SCS pulses configured to form a plurality of SCS waveforms inaccordance with SCS therapy parameters; determining, by the processor,an evoked compound action potential (ECAP) amplitude based on an ECAPwaveform resulting from the SCS therapy parameters; increasing, by theIPG, at least one of the SCS therapy parameters; iteratively repeatingthe delivering, determining and increasing until the ECAP amplitudeexhibits a downward trend divergence; and defining, by the processor, astimulation threshold based on the ECAP amplitude at the downward trenddivergence.
 22. The method of claim 21, further comprising: during theiteratively repeating, determining, by the processor, an average ECAPamplitude; and reducing, by the processor, the stimulation thresholdwhen an instantaneous ECAP amplitude is lower than the average ECAPamplitude.
 23. The method of claim 21, wherein the SCS waveformscomprise any of a burst stimulation waveform, a tonic stimulationwaveform, a biphasic stimulation waveform, or any combination thereof.24. The method of claim 21, further comprising determining, by theprocessor, that the ECAP amplitude exhibits the downward trenddivergence, wherein the determining comprises: comparing, by theprocessor, an ECAP amplitude corresponding to an Nth iteration of theiteratively repeating with an average ECAP amplitude determined based ona plurality of iterations of the iteratively repeating that occurredprior to the Nth iteration
 25. The method of claim 24, wherein theplurality of the iterations corresponds to at least three iterations.26. The method of claim 21, further comprising: recording, by sensingcircuitry of the IPG, an ECAP waveform based on ECAP measurements onto astimulation database; and wirelessly transmitting ECAP data to anexternal device.
 27. The method of claim 26, wherein the ECAP datacomprises amplitude values corresponding to one or more ECAP waveforms28. The method of claim 21, further comprising measuring, by sensingcircuitry of the IPG, an ECAP waveform proximate to an Aβ sensory fiber.29. The method of claim 21, further comprising determining, by theprocessor, a stimulation baseline.
 30. A system for determining astimulation threshold for closed loop spinal cord stimulationcomprising: a lead having at least one lead electrode, the leadconfigured to be implanted at a target position proximate to or withinnerve tissue of interest; and an implantable pulse generator (IPG)coupled to the lead, the IPG configured to: deliver a plurality of SCSpulses to the at least one electrode in accordance with SCS therapyparameters, wherein each SCS pulse of the plurality of SCS pulses formSCS waveforms; measure a plurality of evoked compound action potential(ECAP) waveforms, each ECAP waveform of the plurality of ECAP waveformscorresponding to an SCS pulse of the plurality of SCS pulses; determineone or more slopes of one or more ECAP waveforms of the plurality ofECAP waveforms; determine that a stimulation threshold has been reachedin response to identifying a decrease in a magnitude of the one or moreof the slopes, wherein the decrease in the magnitude of the one or moreof the slopes indicates overstimulation of neurons of nerve tissue ofinterest.
 31. The system of claim 30, wherein the IPG is furtherconfigured to compare the magnitude of the one or more slopes, whereinthe one or more slopes correspond to a ratio of voltage change versus atime change of at least one ECAP waveform of the plurality of ECAPwaveforms at a predetermined baseline, and wherein the predeterminedbaseline corresponds to a ground of the system.
 32. The system of claim30, wherein the lead comprises a plurality of electrodes, and whereinone or more of the plurality of electrodes are configurable to a cathodestate, and wherein others of the one or more of the plurality ofelectrodes are configurable to an anode state.
 33. The system of claim30, wherein the, for each ECAP waveform of the plurality of ECAPwaveforms, the IPG is further configured to determine a time delaybetween a stimulation spike of the ECAP waveform and one or morefiducial points of the ECAP waveform.
 34. The system of claim 30,wherein the IPG is configured to transmit ECAP data to an externaldevice, wherein the ECAP data includes parameters corresponding to theplurality of ECAP waveforms.
 35. A non-transitory computer-readablemedium comprising instructions that, when executed by a processor of animplantable pulse generator (IPG), cause the processor to performoperations comprising: delivering a series of SCS pulses to nerve tissueof interest, the series of SCS pulses configured to form a plurality ofSCS waveforms in accordance with SCS therapy parameters, wherein the SCSpulses are delivered to the nerve tissue of interest via at least onelead electrode of a lead coupleable to the IPG, the at least one leadelectrode configured to be implanted at a target position proximate toor within the nerve tissue of interest; determining an evoked compoundaction potential (ECAP) amplitude based on an ECAP waveform resultingfrom the SCS pulses; increasing one or more of the SCS therapyparameters; iteratively repeating the delivering, determining andincreasing until the ECAP amplitude exhibits a downward trenddivergence; and defining a stimulation threshold based on the ECAPamplitude at the downward trend divergence.
 36. The IPG of claim 35,wherein the SCS therapy parameters comprise an amplitude of the SCSpulses, a pulse width of the SCS pulses, and a number of the SCS pulses.37. The IPG of claim 35, the operations further comprising: determiningthe ECAP amplitude based on a peak during a predetermined time period ofthe ECAP waveform with respect to a baseline.
 38. The IPG of claim 35,the operations further comprising: defining the stimulation thresholdbased on a combination of electrical characteristics of the SCS pulsesat the trend divergence in addition to the ECAP amplitude.
 39. The IPGof claim 35, the operations further comprising: transmitting, bycommunication circuitry of the IPG, an alert notification indicatingthat the stimulation threshold is defined.
 40. The IPG of claim 35, theoperations further comprising: after defining the stimulation threshold,delivering a series of SCS pulses that have an amplitude at or below thestimulation threshold.